Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens
Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens
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DOI：
10.1016/j.euroneuro.2008.02.006
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发表时间：
2008-07-01
影响因子：
5.6
通讯作者：
Engel, Jorgen A.
中科院分区：
文献类型：
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作者：
Jerlhag, Elisabet;Egecioglu, Emil;Engel, Jorgen A.
此前，我们报道了促食欲肽 ghrelin 激活胆碱能-多巴胺能奖赏 [ink，涉及烟碱乙酰胆碱受体 (nAChR)。 nAChR的α(3)-α(7)和β(2)-β(4)亚基可以组合成五聚体nAChR，具有不同的功能作用。目前的实验表明，生长素释放肽的运动刺激作用，无论是进入后背被盖区（LDTg）还是腹侧被盖区（VTA），都是通过腹侧被盖nAChR介导的，但α（4）β（2）*（使用二氢-β-赤霉素）和α（7）*（使用甲基lycaconitine）都不是介导的 似乎涉及亚型。另一方面，VTA 中的 alpha(3)beta(2)*、beta(3)* 和/或 alpha(6)*（使用 a.-芋螺毒素 MII）亚型介导 ghrelin 的刺激和 DA 增强作用，这是 ghrelin 与乙醇共有的模式 (n = 5-8)。放射性配体结合实验表明，ghrelin 不会直接干扰 nAChR (n=26)。因此，我们建议α(3)β(2)*、β*和/或α(6)*亚型可能是治疗成瘾行为的药理学靶点；包括强迫性暴饮暴食和酗酒。 (c) 2008 Elsevier B.V. 和 ECNP。版权所有。
Previously, we have reported that the orexigenic peptide ghrelin activates the cholinergic-dopaminergic reward [ink, involving nicotinic acetylcholine receptors (nAChR). The alpha(3)-alpha(7) and beta(2)-beta(4) subunits of the nAChR can be combined into pentameric nAChRs, with different functional roles. The present experiments show that the locomotor stimulatory effects of ghrelin, either into laterodorsal tegmental area (LDTg) or ventral tegmental area (VTA), are mediated via ventral tegmental nAChR, but neither the alpha(4)beta(2)* (using dihydro-beta-erythroidine) nor the alpha(7)* (using methyllycaconitine) subtypes appears to be involved. On the other hand, the alpha(3)beta(2)*, beta(3)*, and/or alpha(6)* (using a.-conotoxin MII) subtypes in the VTA mediate the stimulatory and DA-enhancing effects of ghrelin, a pattern that ghrelin shares with ethanol (n= 5-8). Radioligand-binding experiments shown that ghrelin does not interfere directly with nAChRs (n=26). We therefore suggest that the alpha(3)beta(2)*, beta* and/or alpha(6)* subtypes might be pharmacological targets for treatment of addictive behaviours; including compulsive overeating and alcoholism. (c) 2008 Elsevier B.V. and ECNP. All rights reserved.